研究 2-Cl-4,5-MDMA 苯乙胺对青少年和成年雄性大鼠神经化学和行为影响的特征。

Characterization of the Neurochemical and Behavioral Effects of the Phenethylamine 2-Cl-4,5-MDMA in Adolescent and Adult Male Rats.

机构信息

Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.

Institute of Neuroscience, National Research Council of Italy, Cagliari, Italy.

出版信息

Int J Neuropsychopharmacol. 2024 May 1;27(5). doi: 10.1093/ijnp/pyae016.

DOI:10.1093/ijnp/pyae016

PMID:38546531

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11120233/

Abstract

BACKGROUND

The proliferation of novel psychoactive substances (NPS) in the drug market raises concerns about uncertainty on their pharmacological profile and the health hazard linked to their use. Within the category of synthetic stimulant NPS, the phenethylamine 2-Cl-4,5-methylenedioxymethamphetamine (2-Cl-4,5-MDMA) has been linked to severe intoxication requiring hospitalization. Thereby, the characterization of its pharmacological profile is urgently warranted.

METHODS

By in vivo brain microdialysis in adolescent and adult male rats we investigated the effects of 2-Cl-4,5-MDMA on dopamine (DA) and serotonin (5-HT) neurotransmission in two brain areas critical for the motivational and rewarding properties of drugs, the nucleus accumbens (NAc) shell and the medial prefrontal cortex (mPFC). Moreover, we evaluated the locomotor and stereotyped activity induced by 2-Cl-4,5-MDMA and the emission of 50-kHz ultrasonic vocalizations (USVs) to characterize its affective properties.

RESULTS

2-Cl-4,5-MDMA increased dialysate DA and 5-HT in a dose-, brain area-, and age-dependent manner. Notably, 2-Cl-4,5-MDMA more markedly increased dialysate DA in the NAc shell and mPFC of adult than adolescent rats, while the opposite was observed on dialysate 5-HT in the NAc shell, with adolescent rats being more responsive. Furthermore, 2-Cl-4,5-MDMA stimulated locomotion and stereotyped activity in both adolescent and adult rats, although to a greater extent in adolescents. Finally, 2-Cl-4,5-MDMA did not stimulate the emission of 50-kHz USVs.

CONCLUSIONS

This is the first pharmacological characterization of 2-Cl-4,5-MDMA demonstrating that its neurochemical and behavioral effects may differ between adolescence and adulthood. These preclinical data could help understanding the central effects of 2-Cl-4,5-MDMA by increasing awareness on possible health damage in users.

摘要

背景

新型精神活性物质（NPS）在毒品市场中的泛滥引起了人们对其药理学特征和使用相关健康危害的不确定性的关注。在合成兴奋剂 NPS 类别中，苯乙胺 2-Cl-4,5-亚甲二氧基甲基苯丙胺（2-Cl-4,5-MDMA）已被证明与需要住院治疗的严重中毒有关。因此，迫切需要对其药理学特征进行描述。

方法

通过在青少年和成年雄性大鼠的体内脑微透析，我们研究了 2-Cl-4,5-MDMA 对两个对药物的动机和奖赏特性至关重要的脑区，即伏隔核壳和内侧前额叶皮层（mPFC）中的多巴胺（DA）和 5-羟色胺（5-HT）神经传递的影响。此外，我们评估了 2-Cl-4,5-MDMA 引起的运动和刻板行为以及 50-kHz 超声发声（USVs）的发射，以描述其情感特性。

结果

2-Cl-4,5-MDMA 以剂量、脑区和年龄依赖的方式增加了透析液中的 DA 和 5-HT。值得注意的是，2-Cl-4,5-MDMA 对成年大鼠伏隔核壳和 mPFC 中的 DA 透析液的影响比青少年大鼠更为明显，而在伏隔核壳中的 5-HT 透析液中则相反，青少年大鼠的反应更为强烈。此外，2-Cl-4,5-MDMA 刺激了青少年和成年大鼠的运动和刻板行为，尽管在青少年大鼠中更为明显。最后，2-Cl-4,5-MDMA 并没有刺激 50-kHz USVs 的发射。